Abstract：
:Cocaine is eliminated and detoxified principally through the metabolism of nonspecific plasma and tissue esterases. Microsomal oxidative metabolism is of importance in cocaine N-demethylation, this being a principal pathway of cocaine bioactivation and hepatotoxicity. The contribution of different cytochrome P450 (CYP) enzymes to cocaine N-demethylase activity was studied in vitro with DBA/2 mouse and human liver microsomes, and cocaine hepatotoxicity was examined in vivo in DBA/2 male mice. Species dependent enzyme kinetics was observed. Cocaine N-demethylase displayed two Km values in murine liver (40-60 microM and 2-3 mM), whereas only one Km value was observed in human liver microsomes (2.3-2.7 mM). We suggest that CYP3A plays a prominent role in the N-demethylation of cocaine for the following reasons: (i) pregnenolone-16 alpha-carbonitrile, an inducer of CYP3As increases cocaine N-demethylase in parallel with testosterone 6 beta-hydroxylase activity and immunoreactive 3A protein in mouse liver; (ii) human and mouse cocaine N-demethylase and testosterone 6 beta-hydroxylase activities can be inhibited by triacetyloleandomycin, cannabidiol, or gestodene, all selective inhibitors of CYP3A P450s; (iii) antibodies directed against P450s within subfamilies 1A, 2A, 2B, 2C, or 2E inhibited cocaine N-demethylase activity only marginally, and finally, (iv) treatment of mice with triacetyloleandomycin or cannabidiol in vivo significantly attenuated the cocaine-elicited hepatotoxicity as assessed by the serum alanine aminotransferase activity and liver histology in parallel with decreased cocaine N-demethylase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Pellinen P,Honkakoski P,Stenbäck F,Niemitz M,Alhava E,Pelkonen O,Lang MA,Pasanen Mdoi
10.1016/0926-6917(94)90078-7subject
Has Abstractpub_date
1994-01-03 00:00:00pages
35-43issue
1eissn
0014-2999issn
1879-0712journal_volume
270pub_type
杂志文章abstract：:Two highly selective mu-opioid receptor agonists, endomorphin-1 and endomorphin-2, have been identified and postulated to be endogenous ligands for mu-opioid receptors. Intrathecal (i.t.) administration of endomorphin-1 and endomorphin-2 at doses from 0.039 to 5 nmol dose-dependently produced antinociception with the ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01238-9
更新日期：2001-09-21 00:00:00
abstract：:In guinea pig papillary muscle, the rate of electrical stimulation (0.1-2 Hz) strongly influenced the effects of the Anemonia sulcata toxin ATX II on action potential duration (APD) and contractile force. In the concentration range studied (10-8-10-7 M), ATX II always produced a larger prolongation in APD at low rates...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90632-x
更新日期：1982-04-23 00:00:00
abstract：:Soluble guanylate cyclase, a heterodimer consisting of an alpha- and a heme-containing beta-subunit, is the major receptor for the biological messenger nitric oxide (NO) and is involved in various signal transduction pathways. The heme moiety of the enzyme is bound between the axial heme ligand histidine(105) and the ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.02.046
更新日期：2005-04-18 00:00:00
abstract：:The weak aminotetralin stimulants, (+)-AJ 76, cis-(+)-5-methoxy-1-methyl-2-(n-propylamino)tetralin and (+)-UH 232, cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, were tested for their effects on firing rates of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNPC). (+)-AJ 76 and (+)-UH 232 a...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90280-j
更新日期：1990-07-03 00:00:00
abstract：:Using microscopic fluorometry and fura-2-loaded cultured bovine aortic endothelial cells, we determined the effects of captopril, an angiotensin converting enzyme (ACE) inhibitor, on bradykinin-induced Ca2+ transients in endothelial cells. In the presence of extracellular Ca2+, 10(-9) M bradykinin induced an early ris...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(93)90018-5
更新日期：1993-01-15 00:00:00
abstract：:We have examined the effects of chronic gentamicin treatment on arginine8-vasopressin (AVP)-dependent cyclic AMP (cAMP) metabolism in rat medullary collecting tubules (oMCT) and medullary thick ascending limbs of Henle's loop (mTALH). Gentamicin attenuated AVP-stimulated cAMP accumulation to a greater extent in the mT...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)94186-2
更新日期：1990-12-04 00:00:00
abstract：:Endothelial dysfunction is associated with a reduced bioavailability of nitric oxide (NO). In this study, the effects of 17β-estradiol supplement on endothelial function were examined in ovariectomized (OVX) rats following long-term inhibition of NO synthases with L-NAME. Female Sprague Dawley rats were ovariectomized...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.173275
更新日期：2020-09-05 00:00:00
abstract：:Painful diabetic neuropathy is a common complication of diabetes mellitus, which often makes the patients suffer from severe hyperalgesia and allodynia. Thus far, the treatment of painful diabetic neuropathy remains unsatisfactory. Metformin, which is the first-line drug for type-2 diabetes, has been proved to attenua...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.06.010
更新日期：2015-10-05 00:00:00
abstract：:The present study shows that the GABAB positive allosteric modulators (PAMs) CGP7930 and GS39783 stimulate extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) signalling in cells that do not express functional GABAB receptors. In human SH-SY5Y neuroblastoma cells, CGP7930 and GS39783 induced a time- and co...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2016.11.030
更新日期：2017-01-05 00:00:00
abstract：:The spinal cord dorsal horn contains neural mechanisms which can greatly facilitate pain. It is well established that excitatory amino acids, aspartate and glutamate, are involved in the spinal transmission of nociceptive information and in the development of hyperalgesia. In the present study, intrathecal (i.t.) admi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(96)00145-8
更新日期：1996-06-03 00:00:00
abstract：:Foot shocks applied to the rat on a grid floor caused brain noradrenaline depletion. Hemicholinium-3 injected intracerebroventricularly (i.c.v.) blocked the noradrenaline depletion and this blockade was reversed by choline (i.c.v.). Physostigmine (i.c.v.) had different effects according to the age of the rats: "young"...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(77)90067-x
更新日期：1977-08-01 00:00:00
abstract：:Previous results provided evidence for an inhibitory GABAergic influence on the dopamine neurons of the rat retina, without proving that endogenous GABA physiologically regulates the activity of these cells. We injected picrotoxinin intraocularly to dark-adapted rats and measured retinal dopamine turnover. Dopamine wa...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90473-8
更新日期：1981-01-29 00:00:00
abstract：:The quantitative [14C]2-deoxyglucose autoradiographic technique was applied to the measurement of the cerebral metabolic effects of adenosine A1 and A2 receptor agonists and antagonists in adult rats. The adenosine A1 receptor agonist and antagonist, 2-chloro-N6-cyclopentyladenosine (CCPA) and 8-cyclopentyl-1,3-diprop...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90057-4
更新日期：1994-06-02 00:00:00
abstract：:The analgesic effect of cyclazocine microinjected into the diencephalon of rats was studied by using the bradykinin-induced flexor reflex test. The dorsal portion of the medial hypothalamic area was sensitive to cyclazocine with respect to the production of analgesia (ED50 2.6 micrograms/rat). Microinjections of morph...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90119-0
更新日期：1985-04-23 00:00:00
abstract：:Prostaglandin D2 (PGD2) exerts its actions on two G protein-coupled receptors, the prostanoid DP receptor and CRTH2 (chemoattractant homologous receptor expressed on TH2 cells). Here, we characterize the regulation of the signaling and trafficking of the prostanoid DP receptor and CRTH2. Time-course and dose-response ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.11.058
更新日期：2007-02-28 00:00:00
abstract：:The Ah receptor (AhR) mediates many, if not all, of the toxic and biological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related halogenated aromatic hydrocarbons. Although wide variations in species sensitivity to these compounds have been observed, numerous biochemical and physiochemical charac...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(92)90016-6
更新日期：1992-09-01 00:00:00
abstract：:Heparin is a natural polymer widely used in medicine especially during the treatment of cardiovascular diseases since it is a potent blood anticoagulant. In case of emergency, e.g., massive hemorrhage, the anticoagulant activity of heparin has to be quickly stopped by the administration of a heparin reversing agent. C...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.04.037
更新日期：2012-07-05 00:00:00
abstract：:The intravenous infusion of catecholamines to rats induced a dose dependent increase of immunoreactive beta-endorphin (beta-Endi) in plasma. The ED50 values of 1-epinephrine and 1-isoproterenol were 110 and 100 ng/kg X min respectively. 1-Propranolol, but not d-propranolol prevented the effect of 1-epinephrine. Infusi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90303-4
更新日期：1981-06-10 00:00:00
abstract：:The present studies were carried out to analyze the neurochemical and behavioral effects of peripheral sigma ligand administration in the rat. Based upon previous studies which showed an increase in turning behavior following unilateral intranigral administration of sigma ligands, we determined the effects of two sigm...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90456-r
更新日期：1993-02-09 00:00:00
abstract：:The interaction of phencyclidine, dexoxadrol, their analogs and stereoisomers with phencyclidine receptors was compared to their ability to induce stereotyped behavior and ataxia after i.c.v. administration to rats. The order of potency for binding to phencyclidine receptors revealed that among the stereoisomers of ph...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90386-9
更新日期：1986-02-11 00:00:00
abstract：:Bone marrow mesenchymal stem cells (MSCs) have been shown great potential for cardiac regeneration. However the therapeutic efficiency has become a major obstacle due to the poor survival of transplanted MSCs in ischemic cardiac tissue. Previous studies reported that melatonin could protect many different types of cel...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.09.033
更新日期：2015-02-05 00:00:00
abstract：:The effects of delta9-THC and its ethanol vehicle on pilocarpine-induced parotid gland secretions were investigated in rats. Single doses of delta9-THC (1, 2.5, 5 and 10 mg/kg) or 95% ethanol were administered i.v. prior to pilocarpine stimulation of saliva. Total flow, alpha-amylase and cation content of the induced ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(76)90071-6
更新日期：1976-12-01 00:00:00
abstract：:Hypoxia-inducible factor prolyl hydroxylases (PHDs) inhibitor stabilizes hypoxia inducible factor alpha, which increases erythropoietin (EPO) expression via the hypoxia response element. Therefore, PHDs inhibitors have been developed as novel therapeutic agents for anemia. Here, we characterize the in vitro and in viv...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2018.08.044
更新日期：2018-11-05 00:00:00
abstract：:The specific binding of [3H]threo-(+/-)-methylphenidate to membranes prepared from rat striatum was significantly reduced following either surgical lesions of the medial forebrain bundle or intracerebroventricular administration of 6-hydroxydopamine. The decrease in the density of [3H]threo-(+/-)-methylphenidate bindi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90724-1
更新日期：1985-01-22 00:00:00
abstract：:Local administration of amitriptyline into the rat hindpaw produces peripheral antinociception; this is reduced by adenosine receptor antagonists and appears to involve endogenous adenosine. The present study used peripheral microdialysis: (a) to determine whether amitriptyline could enhance extracellular tissue level...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.06.030
更新日期：2005-08-22 00:00:00
abstract：:The effects of MCI-154, a cardiotonic agent which has direct effects on cardiac myofilaments, on postischemic contractile dysfunction were studied in dog heart subjected to a 30-min occlusion of the left anterior descending coronary artery followed by reperfusion, and compared with the effects of milrinone and dobutam...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90053-s
更新日期：1991-01-10 00:00:00
abstract：:FR 172357, a new non-peptide antagonist of the kinin B(2) receptor was tested in three isolated vessels, the human umbilical vein, the rabbit jugular vein, and the pig coronary artery, to evaluate its antagonistic activities against bradykinin. FR 172357 displaced to the right the concentration-response curves of brad...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00711-6
更新日期：1999-12-10 00:00:00
abstract：:In cases of severe human scorpion envenoming, lung injury is a common finding and frequently the cause of death. In the rat, two distinct mechanisms account for oedema following the intravenous injection of the venom -- acute left ventricular failure resulting from a massive release of catecholamines and an increase i...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00382-9
更新日期：1999-07-09 00:00:00
abstract：:Beat-to-beat alternations of the cardiac monophasic action potential, known as electrical alternans, were studied at drug concentrations that have known arrhythmogenic outcomes. Electrical alternans were elicited from the heart of anesthetized guinea pigs, both in the absence and presence of drugs that inhibit the del...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2003.12.028
更新日期：2004-02-20 00:00:00
abstract：:Acetyl-CoA acetyltransferase (1-O-alkyl-sn-glycero-3-phosphocholine) is a key enzyme in paf-acether biosynthesis. Its immunological activation as related to paf-acether formation was investigated in mast cells derived from mouse bone marrow. The action of ketotifen, a prophylactic anti-asthma drug, on the antigen-indu...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90511-5
更新日期：1987-12-01 00:00:00
